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Journal of Nanoparticle Research

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01-12-2022 | Research paper

AS1411 aptamer improves therapeutic efficacy of PEGylated nanoliposomes loaded with gefitinib in the mice bearing CT26 colon carcinoma

Authors: Hamid Tanzadehpanah, Hanie Mahaki, Hamed Manoochehri, Meysam Soleimani, Rezvan Najafi

Published in: Journal of Nanoparticle Research | Issue 12/2022

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Abstract

In this work, a tumor-targeting liposome containing anti-nucleolin aptamer AS1411 (Apt-Lip-GEF) was developed to deliver gefitinib (GEF) for the treatment of colon cancer. The prepared liposomes were characterized using their morphological properties, size dispersity, zeta potential, encapsulation efficiency, and release properties. The anti-tumor effects of Lip-GEF and Apt-Lip-GEF were measured using cytotoxicity and apoptosis-induced and quantitative real-time PCR. Furthermore, in vivo experiments were evaluated in BALB/c mice bearing CT26 colon carcinoma. Binding of AS1411 to the surface of liposomes was confirmed by gel electrophoresis. The encapsulation efficiency of the Lip-GEF and Apt-Lip-GEF obtained 91 ± 7.1% and 86 ± 5.4%, respectively, and the in vitro release of GEF from both formulations was at acceptable range. Fluorescence microscopy and flow cytometry confirmed the enhanced cellular uptake of AS1411-targeted liposomes in the CT26 cells. Cytotoxicity assay indicated that Apt-Lip-GEF had higher anti-proliferative activity than CT26 cells as positive nucleolin compared to HEK293 as negative nucleolin. At equal concentrations (98 µM), Apt-Lip-GEF was more successful than Lip-GEF in causing apoptosis and cell necrosis. The upregulation of BAX and the downregulation of PIK and AKT as well as BCL2 were observed after treatment with Apt-Lip-GEF in CT26 cells, using qRT-PCR analysis. In cancer model mice, treatment with Apt-Lip-GEF compared with free GEF showed a significant reduction in tumor growth; moreover, the lowest rates of weight change were observed in Apt-Lip-GEF group. Modified nanoliposome acts as a successful delivery system for gefitinib and has high potential for the treatment of colorectal cancer.

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Title: AS1411 aptamer improves therapeutic efficacy of PEGylated nanoliposomes loaded with gefitinib in the mice bearing CT26 colon carcinoma
Authors: Hamid Tanzadehpanah
Hanie Mahaki
Hamed Manoochehri
Meysam Soleimani
Rezvan Najafi
Publication date: 01-12-2022
Publisher: Springer Netherlands
Published in: Journal of Nanoparticle Research / Issue 12/2022
Print ISSN: 1388-0764
Electronic ISSN: 1572-896X
DOI: https://doi.org/10.1007/s11051-022-05630-0

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